PB1736: CLINICAL ANALYSIS OF VENETOCLAX-BASED IN THE TREATMENT OF ADULT RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Jing LI, Zhaoping Gan, Jun Luo, Yongrong Lai
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: The prognosis of adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) is dismal. A frequent option in such circumstances is to obtain a new complete remission (CR) as a bridge to perform allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is the best prospect for cure. However, with standard chemotherapy induction, CR rates are 30% to 46% in the first salvage setting and 18% to 25% in the second salvage setting. Therefore, in order to improve the survival of these patients, a key issue is how to increase the CR rate of re-induction therapy. Aims: The purpose of this study was to find a high CR rate and economical chemotherapy regimen for R/R B-ALL patients and to improve the remission rate of re-induction chemotherapy in R/R B-ALL patients. The venetoclax-based regimen further creates opportunities for allogeneic hematopoietic stem cell transplantation. Methods: We collected 7 adult R/R B-ALL patients from May 2022 to June 2023. Adult R/R B-ALL patients were given with venetoclax-based regimen (venetoclax 100mg/d1,200mg/d2,400mg/d3-28, MTX 100mg/m2/d1, d15, VCR 1mg/d1, d8, d15,d22,Asp 2500u/m2/d2,d16,Dex 20mg/d1-4,d15-18). In addition, patients with ph-positive B-ALL were treated with venetoclax in combination with orebatinib. We collected general information, clinical efficacy, and toxicity of all patients. The collected parameters were further incorporated into descriptive statistical analysis and survival analysis. Results: A total of seven patients were included in the analysis. They were all in the high-risk group. The average line of prior treatments was 1.4(1-3). All patients did not receive allo-HSCT after venetoclax-based salvage regimen for economic reasons. The overall response rate (ORR) was as high as 85.7% (6/7), and CR rate was 71.4%. The median follow-up time was 124(11-282) days. The OS rate was 71.4% (5/7) and the event-free survival (EFS) rate was 14.3% (1/7). In addition, the median duration of remission (DOR) was 76 (13-104) days. The major treatment-related adverse events were myelosuppression and infection. Summary/Conclusion: Venetoclax-based salvage regimen demonstrated significantly higher CR rates compared to historical data with conventional chemotherapy. Similar CR rates with venetoclax-based regimen were comparable to blinatumomab and inotuzumab ozogamicin. However, venetoclax was more acceptable in China because it was less expensive. None of the patients in our group received allo-HSCT when achieving CR, which affected EFS and OS. Nevertheless, our data suggested that the venetoclax-based regimen offered an option for R/R B-ALL with a high probability of CR. Table Patient disease characteristics, response and toxicity. - Patient Number Disease status at enrollment Age/Sex Cytogenetics NGS and PCR Mutation Findings Prior Therapies line Response Toxicity 1 R/R 34/M Complex karyotype EP300-ZNF384, NRAS 2 MRD-CRi Febrile neutropenia，intestinal infection，thrombocytopenia，anemia 2 R/R 17/M Complex karyotype IKZF1 1 CRi Febrile neutropenia，oral infection，thrombocytopenia，anemia 3 R/R 58/F Complex karyotype BCR-ABL1,PAX5,IKZF1 2 MRD+CRi Febrile neutropenia， pulmonary infection，thrombocytopenia，anemia 4 R/R 46/F t(9;22) BCR/ABL1 1 MRD-CRi thrombocytopenia，anemia 5 Refractory 66/F normal E2A-PBX1, NRAS 1 PR Febrile neutropenia，bloodstream infection(candida tropicalis)，infectious shock, thrombocytopenia，anemia 6 R/R 28/M normal NRAS, IKZF1 1 MRD+CR Febrile neutropenia，bloodstream infection(escherichia coli)，infectious shock,thrombocytopenia，anemia 7 Refractory 63/M Complex karyotype JAK2, IDH 2 UNKNOW neutropenia， thrombocytopenia，anemia, tumor cytolysis syndrome Keywords: relapsed/refractory, Venetoclax, B cell, ALL